Abstract
There is a large variation in caloric intake and macronutrient preference between individuals and between ethnic groups, and these food intake patterns show a strong heritability. The transition to new food sources during the agriculture revolution around 11,000 years ago probably created selective pressure and shaped the genome of modern humans. One major player in energy homeostasis is the appetite-stimulating hormone neuropeptide Y, in which the stimulatory capacity may be mediated by the neuropeptide Y receptors 1, 2 and 5 (NPY1R, NPY2R and NPY5R). We assess association between variants in the NPY1R, NPY2R and NPY5R genes and nutrient intake in a cross-sectional, single-center study of 400 men aged 40 to 80 years, and we examine whether genomic regions containing these genes show signatures of recent selection in 270 HapMap individuals (90 Africans, 90 Asians, and 90 Caucasians) and in 846 Dutch bloodbank controls. Our results show that derived alleles in NPY1R and NPY5R are associated with lower carbohydrate intake, mainly because of a lower consumption of mono- and disaccharides. We also show that carriers of these derived alleles, on average, consume meals with a lower glycemic index and glycemic load and have higher alcohol consumption. One of these variants shows the hallmark of recent selection in Europe. Our data suggest that lower carbohydrate intake, consuming meals with a low glycemic index and glycemic load, and/or higher alcohol consumption, gave a survival advantage in Europeans since the agricultural revolution. This advantage could lie in overall health benefits, because lower carbohydrate intake, consuming meals with a low GI and GL, and/or higher alcohol consumption, are known to be associated with a lower risk of chronic diseases.
Highlights
One major player in energy homeostasis is the appetitestimulating hormone neuropeptide Y (NPY) [1]
In this study we investigated the role of single nucleotide polymorphisms (SNPs) in NPY1R, NPY2R and NPY5R genes in the total and nutrient-specific energy intake in a Dutch study population of 400 healthy older men
We show that derived alleles in NPY1R and NPY5R are associated with lower carbohydrate intake, mainly because of a lower consumption of mono- and disaccharides
Summary
One major player in energy homeostasis is the appetitestimulating hormone neuropeptide Y (NPY) [1]. The effect of NPY is mediated by the neuropeptide Y receptors (NPYRs) [3]. The Y1, Y2, and Y5 receptors (NPY1R, NPY2R, NPY5R) appear to be candidates for mediating the appetite stimulatory capacity of NPY[4,5] through binding of NPY. These are receptors in the arcuate and paraventricular nuclei of the hypothalamus. Variants in genes coding for these receptors may influence energy intake, which could influence an individual’s susceptibility to becoming obese and developing T2D. We have previously pinpointed NPY1R, NPY2R and NPY5R as positional candidate genes for both obesity and T2D [6]
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